Polycystic ovary syndrome (PCOS) is a common metabolic disorder in women. To identify causative genes, we conducted a genome-wide association study (GWAS) of PCOS in Han Chinese. The discovery set ...included 744 PCOS cases and 895 controls; subsequent replications involved two independent cohorts (2,840 PCOS cases and 5,012 controls from northern Han Chinese; 498 cases and 780 controls from southern and central Han Chinese). We identified strong evidence of associations between PCOS and three loci: 2p16.3 (rs13405728; combined P-value by meta-analysis Pmeta = 7.55 × 10−21, odds ratio (OR) 0.71); 2p21 (rs13429458, Pmeta = 1.73 × 10−23, OR 0.67); and 9q33.3 (rs2479106, Pmeta = 8.12 × 10−19, OR 1.34). These findings provide new insight into the pathogenesis of PCOS. Follow-up studies of the candidate genes in these regions are recommended.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
The protozoan Trypanosoma cruzi almost invariably establishes life-long infections in humans and other mammals, despite the development of potent host immune responses that constrain parasite ...numbers. The consistent, decades-long persistence of T. cruzi in human hosts arises at least in part from the remarkable level of genetic diversity in multiple families of genes encoding the primary target antigens of anti-parasite immune responses. However, the highly repetitive nature of the genome-largely a result of these same extensive families of genes-have prevented a full understanding of the extent of gene diversity and its maintenance in T. cruzi. In this study, we have combined long-read sequencing and proximity ligation mapping to generate very high-quality assemblies of two T. cruzi strains representing the apparent ancestral lineages of the species. These assemblies reveal not only the full repertoire of the members of large gene families in the two strains, demonstrating extreme diversity within and between isolates, but also provide evidence of the processes that generate and maintain that diversity, including extensive gene amplification, dispersion of copies throughout the genome and diversification via recombination and in situ mutations. Gene amplification events also yield significant copy number variations in a substantial number of genes presumably not required for or involved in immune evasion, thus forming a second level of strain-dependent variation in this species. The extreme genome flexibility evident in T. cruzi also appears to create unique challenges with respect to preserving core genome functions and gene expression that sets this species apart from related kinetoplastids.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
In China's latest school funding reform, the central government remarkably increases input in basic education. However, this fiscal re-centralisation of education provision is implemented through a ...highly decentralised administration structure and yet local governments have long been criticised by the public for their inefficiency and misconduct. This paper depicts a snapshot of how school funding policies are practiced in rural China at grassroot government levels. It also discusses the implication of such praxis, drawing on the concept of equity underpinning Australia's recent review on school funding. Selecting Shandong Province as a case study, this paper firstly analyses publicly accessible online documents on funding policies, released by the state, provincial, prefecture and county governments, to map out the procedures and models of school funding in rural areas. The second set of data was collected through interviews and focus groups with officials from local education authorities and school principals, so as to create a real-life portrait of policy implementation. This empirical study discovers that waste of resource coexists with insufficient funding: biased funding reinforces school hierarchy, improper means are employed to identify students with financial needs, disabled children have strikingly limited access to education, and students with learning difficulties are largely ignored. This paper argues these deficiencies can be explained by local governments' operational preference. In short, local governments' active involvement in school funding process may have aggravated inequity.
Academics researchers and “citizen scientists” from 22 countries confirmed that yellow mealworms, the larvae of Tenebrio molitor Linnaeus, can survive by eating polystyrene (PS) foam. More detailed ...assessments of this capability for mealworms were carried out by12 sources: five from the USA, six from China, and one from Northern Ireland. All of these mealworms digested PS foam. PS mass decreased and depolymerization was observed, with appearance of lower molecular weight residuals and functional groups indicative of oxidative transformations in extracts from the frass (insect excrement). An addition of gentamycin (30 mg g−1), a bactericidal antibiotic, inhibited depolymerization, implicating the gut microbiome in the biodegradation process. Microbial community analyses demonstrated significant taxonomic shifts for mealworms fed diets of PS plus bran and PS alone. The results indicate that mealworms from diverse locations eat and metabolize PS and support the hypothesis that this capacity is independent of the geographic origin of the mealworms, and is likely ubiquitous to members of this species.
Display omitted
•Consumption of polystyrene (PS) by mealworms observed in 22 countries.•PS degrades in mealworms obtained from 12 locations in the USA, UK and China.•Addition of nutrition enhances survival rate and PS consumption rate.•Antibiotics depresses gut microbes and severely inhibits PS degradation.•PS feeding shifts mealworm gut microbiome.
Display omitted
•3′-SL and 6′-SL attenuated intestinal hypoxic injury in vitro and vivo.•3′-SL and 6′-SL mixture protected intestine against the damage induced by NEC.•3′-SL and 6′-SL mixture ...inhibited the activation of the TLR4/NF-κB pathway.
In premature infants, necrotizing enterocolitis (NEC) is one of the most prevalent diseases among premature infants and has a high mortality rate. Previous studies have shown that human milk oligosaccharides (HMOs) could effectively decrease the incidence of NEC. However, it is not known whether the efficacy of oligosaccharides is related to their structure. We found that among the HMOs, 3′-sialyllactose (3′-SL) and 6′-sialyllactose (6′-SL) significantly restored proliferation, reduced apoptosis, and relieved inflammation of the intestinal cells of neonatal mice under hypoxia. In addition, our findings indicated that 3′-SL and 6′-SL provide protection against NEC-induced intestinal damage by inhibiting the activation of the TLR4/NF-κB pathway. In sum, 3′-SL and 6′-SL, which are formed when Sia monosaccharide is linked to lactose, are HMO components that can effectively alleviate hypoxia-induced damage in NEC and should be considered as a potential nutritional supplement that can be added to infant formula.
Modification of lattice thermal conductivity (κL) of a solid by means of hydrostatic pressure (P) has been a crucially interesting approach that targets a broad range of advanced materials from ...thermoelectrics and thermal insulators to minerals in mantle. Although it is well documented knowledge that thermal conductivity of bulk materials normally increase upon hydrostatic pressure, such positive relationship is seriously challenged when it comes to ceramics with complex crystal structure and heterogeneous chemical bonds. In this paper, we predict an abnormally negative trend dκL/dP < 0 in Y2Si2O7 silicate using density functional theoretical calculations. The mechanism is disclosed as combined effects of slightly decreased group velocity and significantly augmented scattering of heat-carrying acoustic phonons in pressured lattice, which is originated from pressure-induced downward shift of low-lying optic and acoustic phonons. The structural origin of low-lying optic phonons as well as the induced phonon anharmonicity is also qualitatively elucidated with respect to intrinsic bonding heterogeneity of Y2Si2O7. The present results are expected to bring deeper insights for phonon engineering and modulation of thermal conductivity in complex solids with diverging structural flexibility, enormous bonding heterogeneity, and giant phonon anharmonicity.
Nonspecific interactions play a significant role in physiological activities, surface chemical modification, and artificial adhesives. However, nonspecificity sometimes causes sticky problems, ...including surface fouling, decreased target specificity, and artifacts in single-molecule measurements. Adjusting the liquid pH, using protein-blocking additives, adding nonionic surfactants, or increasing the salt concentration are common methods to minimize nonspecific binding to achieve high-quality data. Here, we report that grafting heteromorphic polyethylene glycol (Y-shape PEG) with two inert terminates could noticeably decrease nonspecific binding. As a proof-of-concept, we performed single-molecule force spectroscopy and fluorescence staining imaging experiments to verify the feasibility of Y-shape PEG in blocking nonspecific interactions. Our results indicate that Y-shape PEG could serve as a prominent and efficient candidate to minimize nonspecificity for scientific and biomedical applications.
Spinal cord injury (SCI) is a devastating neurological condition, commonly leading to physical and mental deficiencies, pain, other complications, and even death. Most recently, neural tissue ...engineering (NTE) has fostered the improvement of nerve regeneration after severe SCI, presenting a promising potential in clinic application. Ideal biomaterial scaffolds are undoubtedly the primary focus of NTE, and electrospinning technique has been extensively explored for the design and development of engineered scaffolds for NTE application owing to its simple processing, wide applicability, and huge industrialization potential. Moreover, electrospun nanofibrous scaffolds commonly possess small diameter and high specific surface area compared to traditional microfibrous scaffolds, thus providing beneficial microenvironment. Importantly, the nanofibrous structure of electrospun scaffolds largely resemble the topographic and structural characteristics of native extracellular matrix (ECM), and can effectively promote cell adhesion, growth, migration, proliferation, and even neuronal differentiation, as well as ECM remodeling and neo-tissue regeneration. In this review, we firstly introduce the anatomy of spinal cord and pathological mechanism of SCI. Then, the recent advances in the fabrication and modification of electrospun nanofibrous scaffolds for SCI treatment are summarized. Recent innovative techniques for the generation of aligned nanofibrous scaffolds and 3D anisotropic nanofibrous scaffolds are highlighted. Furthermore, several advanced synergetic approaches by integrating bioactive ingredients, external electrical or magnetic stimulation, and cell therapy with electrospun nanofibrous scaffolds are reviewed. At the end of this review, the challenges and prospects of employing electrospinning-based strategies for the SCI treatment in clinics are deeply discussed and summarized.
Display omitted
•A critical review on advanced electrospinning-based strategies for spinal cord regeneration application.•Introducing the anatomy of spinal cord and pathological mechanism of spinal cord injury (SCI).•Highlighting some innovative electrospinning-based scaffolds for SCI treatment.•Summarizing some synergetic approaches with electrospun nanofibrous scaffolds.•Discussing the challenges and prospects of electrospinning-based strategies for clinical SCI treatment.
Background
Blood-brain barrier (BBB) disruption and gut microbiota dysbiosis play crucial roles in Alzheimer’s disease (AD). Lipopolysaccharide (LPS) stimulation triggered by gut microbial dysbiosis ...is an important factor in BBB disruption and systemic inflammation, but the mechanism of acupuncture regulation of BBB disruption
via
the gut microbiota in AD is not clear.
Objective
The current study evaluated the effect of manual acupuncture (MA) on BBB dysfunction in APP/PS1 mice and examined the mechanism of gut microbiota by acupuncture in AD.
Methods
Acupoints were applied to Baihui (GV20), Yintang (GV29), and Zusanli (ST36) in the MA group. Mice in the manual acupuncture plus antibiotics (MAa) group received antibiotics and acupuncture, while mice in the probiotics (P) group received probiotics. Alterations in spatial learning and memory, the gut microbiota, tightly connected structure and permeability of BBB, and the expression of LPS and inflammatory factors in each group were assessed.
Results
Compared to the normal (N) group, cognitive ability was significantly impaired, the gut microbiota composition was markedly altered, the BBB was significantly disrupted, and the expression of LPS in serum and brain, serum TNF-α, and IL-1β were significantly increased in the AD group (
p
< 0.01). These changes were inhibited in the MA and P groups (
p
< 0.01 or
p
< 0.05), and antibiotics reversed the benign regulatory effects of MA (
p
< 0.01 or
p
< 0.05).
Conclusion
Manual acupuncture benignly modulated the gut microbiota and BBB dysfunction, reduced LPS, TNF-α, and IL-1β. These effects were comparable to probiotics. The decrease in LPS load and systemic inflammation may play important roles in the regulation of BBB dysfunction by acupuncture, and the gut microbiota may be a potential target for the benign regulation of BBB disruption by acupuncture.
This letter investigates the resource allocation and power control for both device-to-device (D2D) pairs and cellular users (CUs) in D2D communication underlaying single-cell cellular networks, where ...multiple D2D pairs can share the same resources with CUs. Our goal is to maximize the sum rate of D2D pairs subject to the rate requirements for all CUs and power requirements for both D2D pairs and the base station. We first give the optimal conditions for the resource allocation of D2D pairs and power control of CUs and then propose an iterative resource allocation and power control algorithm. Numerical results show that the proposed algorithm achieves higher sum rate of D2D pairs than the existing schemes.
PDF
